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Disease Profile

Hypermobile Ehlers-Danlos syndrome

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
1-5 / 10 000

33,100 - 165,500

US Estimated

1-5 / 10 000

51,350 - 256,750

Europe Estimated

Age of onset

All ages

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ICD-10

Q79.6

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

EDS3 (formerly); Ehlers-Danlos syndrome type 3 (formerly); Ehlers-Danlos syndrome, hypermobility type;

Categories

Congenital and Genetic Diseases; Skin Diseases

Summary

Hypermobile Ehlers-Danlos syndrome is an inherited connective tissue disorder that is caused by defects in a protein called collagen. It is generally considered the least severe form of Ehlers-Danlos syndrome (EDS) although significant complications can occur. Common symptoms include joint hypermobility, affecting both large (elbows, knees) and small (fingers, toes) joints; soft, smooth skin that may be slightly elastic (stretchy) and bruises easily; and chronic musculoskeletal (muscle and bone) pain. While hypermobile EDS is regarded as a genetic condition, the genetic cause is unknown as the gene(s) responsible have not been identified. Inheritance is autosomal dominant. Treatment and management is focused on preventing serious complications and relieving associated signs and symptoms.[1][2][3]

Symptoms

The signs and symptoms of hypermobile Ehlers-Danlos syndrome vary but may include:[1][4][5][6]

  • Joint hypermobility affecting both large (elbows, knees) and small (fingers, toes) joints
  • Frequent joint dislocations and subluxations (partial dislocation), often affecting the shoulder, kneecap, and/or temporomandibular joint (joint that connects the lower jaw to the skull)
  • Soft, smooth skin that may be slightly elastic (stretchy) and bruises easily
  • Chronic musculoskeletal (muscle and bone) pain
  • Early-onset osteoarthritis
  • Osteoporosis
  • Gastrointestinal issues such as dysmotility, bloating, nausea, vomiting, heartburn, constipation, or hiatal hernia (which can also cause issues such as heartburn or reflux)
  • Dysfunction of the autonomic nervous system
  • Cardiovascular abnormalities such as mitral valve prolapse or aortic root dilatation (enlargement of the blood vessel that distributes blood from the heart to the rest of the body)
  • Increased risk of pelvic prolapse, painful menstruation (dysmenorrhea), and painful intercourse (dyspareunia) in women
  • Increased risk of pregnancy complications such as premature rupture of membranes or rapid labor and delivery (less than 4 hours)

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Acrocyanosis
Persistent blue color of hands, feet, or parts of face
0001063
Arthralgia
Joint pain
0002829
Elbow dislocation
Dislocations of the elbows
Elbow dislocations

[ more ]

0003042
Fatigue
Tired
Tiredness

[ more ]

0012378
Hip dislocation
Dislocated hips
Dislocation of hip

[ more ]

0002827
Hyperextensible skin
Hyperelastic skin
Skin hyperelasticity
Stretchable skin

[ more ]

0000974
Joint hyperflexibility
Joints move beyond expected range of motion
0005692
Myalgia
Muscle ache
Muscle pain

[ more ]

0003326
Sleep disturbance
Difficulty sleeping
Trouble sleeping

[ more ]

0002360
Vertigo
Dizzy spell
0002321
Wormian bones
Extra bones within cranial sutures
0002645
30%-79% of people have these symptoms
Arrhythmia
Abnormal heart rate
Heart rhythm disorders
Irregular heart beat
Irregular heartbeat

[ more ]

0011675
Constipation
0002019
Decreased nerve conduction velocity
0000762
Depressivity
Depression
0000716
Malabsorption
Intestinal malabsorption
0002024
Migraine
Intermittent migraine headaches
Migraine headache
Migraine headaches

[ more ]

0002076
Nausea and vomiting
0002017
Osteoarthritis
Degenerative joint disease
0002758
Pes planus
Flat feet
Flat foot

[ more ]

0001763
Soft skin
0000977
Thin skin
0000963
5%-29% of people have these symptoms
Abnormal palate morphology
Abnormality of the palate
Abnormality of the roof of the mouth

[ more ]

0000174
Abnormality of the menstrual cycle
0000140
Abnormality of the wrist
Abnormalities of the wrists
0003019
Anorectal anomaly
0012732
Aplasia/Hypoplasia of the abdominal wall musculature
Absent/small abdominal wall muscles
Absent/underdeveloped abdominal wall muscles

[ more ]

0010318
Apnea
0002104
Arterial dissection
0005294
Ascending tubular aorta aneurysm
Bulging of wall of large artery located above heart
0004970
Atypical scarring of skin
Atypical scarring
0000987
Cystocele
Bladder hernia
Dropped bladder

[ more ]

0100645
Decreased fertility
Abnormal fertility
0000144
Epicanthus
Eye folds
Prominent eye folds

[ more ]

0000286
Gastroesophageal reflux
Acid reflux
Acid reflux disease
Heartburn

[ more ]

0002020
Gastrointestinal dysmotility
0002579
Gingival overgrowth
Gum enlargement
0000212
Gingivitis
Inflamed gums
Red and swollen gums

[ more ]

0000230
Inguinal hernia
0000023
Keratoconjunctivitis sicca
Dry eyes
0001097
Keratoconus
Bulging cornea
0000563
Limitation of joint mobility
Decreased joint mobility
Decreased mobility of joints
Limited joint mobility
Limited joint motion

[ more ]

0001376
Microdontia
Decreased width of tooth
0000691
Osteolysis
Breakdown of bone
0002797
Paresthesia
Pins and needles feeling
Tingling

[ more ]

0003401
Ptosis
Drooping upper eyelid
0000508
Scoliosis
0002650
Subcutaneous nodule
Firm lump under the skin
Growth of abnormal tissue under the skin

[ more ]

0001482
Tendon rupture
Rupture of tendons
Ruptured tendon

[ more ]

0100550
Umbilical hernia
0001537
Venous insufficiency
Poorly functioning veins
0005293
Percent of people who have these symptoms is not available through HPO
Autosomal dominant inheritance
0000006
Joint dislocation
Joint dislocations
Recurrent joint dislocations

[ more ]

0001373
Joint hypermobility
Double-Jointed
Flexible joints
Increased mobility of joints

[ more ]

0001382
Joint laxity
Joint instability
Lax joints
Loose-jointedness
Loosejointedness

Cause

Although hypermobile Ehlers-Danlos syndrome is regarded as a genetic condition, the underlying cause (gene or genes responsible) has not been identified.[1][7]

Diagnosis

Hypermobile Ehlers-Danlos syndrome (hEDS) is diagnosed based on the presence of characteristic signs and symptoms because there is no specific test available.[1][8] The following three major criteria should be met:[9]

Criteria 1: Generalized joint hypermobility (small and large joints) which is assessed by using the Beighton Score system and a questionnaire.

Criteria 2: Two or more of the following features must be present (A&B, A&C, B&C, or A&B&C):

    Feature A—systemic manifestations of a more generalized connective tissue disorder (a total of 5 out of 12 must be present)

1. Unusually soft or velvety skin
2. Mild skin hyperextensibility
3. Unexplained striae such as striae distensae or rubrae at the back, groins, thighs, breasts and/or abdomen in adolescents, men or prepubertal women without a history of significant gain or loss of body fat or weight
4. Bilateral piezogenic papules of the heel
5. Recurrent or multiple abdominal hernia(s) (e.g., umbilical, inguinal, crural)
6. Atrophic scarring involving at least two sites and without the formation of truly papyraceous and/or hemosideric scars as seen in classical EDS
7. Pelvic floor, rectal, and/or uterine prolapse in children, men or nulliparous women without a history of morbid obesity or other known predisposing medical condition
8. Dental crowding and high or narrow palate
9. Arachnodactyly, as defined in one or more of the following: (i) positive wrist sign (Steinberg sign) on both sides; (ii) positive thumb sign (Walker sign) on both sides
10. Arm span-to-height ≥1.05
11. Mitral valve prolapse (MVP) mild or greater based on strict echocardiographic criteria
12. Aortic root dilatation with Z-score > +2

Feature B—positive family history, with one or more first-degree relatives independently meeting the current diagnostic criteria for hEDS.

Feature C—musculoskeletal complications (must have at least 1 of 3 ):

1. Musculoskeletal pain in 2 or more limbs, recurring daily for at least 3 months
2. Chronic, widespread pain for ≥3 months
3. Recurrent joint dislocations or frank joint instability, in the absence of trauma (a or b)
  a. Three or more atraumatic dislocations in the same joint or two or more atraumatic dislocations in two different joints occurring at different times
b. Medical confirmation of joint instability at two or more sites not related to trauma

Criteria 3: All these prerequisites must be met: absence of unusual skin fragility, exclusion of other heritable and acquired connective tissue disorders including autoimmune rheumatologic conditions, and exclusion of alternative diagnoses that may also include joint hypermobility due to poor muscle tone (hypotonia) and/or connective tissue laxity.

Other problems (which are not necessarily present) include recurrent joint dislocations, chronic joint/limb pain, and positive family history.[8]

Making the diagnosis can sometimes be complicated by the fact that joint hypermobility is more common in females and young children. Also, joint hypermobility may lessen with age, especially with the development of arthritis or after surgery. In these cases, it would be important to note a past history of joint laxity.[8]

There is a range of conditions which can accompany hEDS, although there is not enough data for them to become part of the diagnostic criteria. While they’re associated with hEDS, they’re not proven to be the result of hEDS and they’re not specific enough to be criteria for diagnosis. Some of these include sleep disturbance, fatigue, postural orthostatic tachycardia, functional gastrointestinal disorders, dysautonomia, anxiety, and depression. These conditions are sometimes more debilitating than the joint symptoms as they often impair daily life, and should be considered and treated.[9]

Treatment

The treatment of hypermobile Ehlers-Danlos syndrome depends on the signs and symptoms present in each person. For example, physical therapy is often recommended to strengthen muscles and improve joint stability. Assistive devices such as braces, wheelchairs, or scooters may be necessary depending on the severity of joint instability. Pain medications may be prescribed to manage severe musculoskeletal (muscle and bone) pain. Affected people may be monitored for the development of osteopenia (low bone density) and aortic root dilatation (enlargement of the blood vessel that distributes blood from the heart to the rest of the body).[1][3][10]

GeneReviews (see below) offers more detailed information regarding the treatment and management of hypermobile EDS.

Please speak to your healthcare provider if you have any questions about your personal medical management plan.

Organizations

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

    Social Networking Websites

    • The Ehlers-Danlos, Marfan and Related CTDs New England/MA Facebook Support Group offers educational and peer support through this forum.
    • RareConnect has an online community for patients and families with this condition so they can connect with others and share their experiences living with a rare disease. The project is a joint collaboration between EURORDIS (European Rare Disease Organisation) and NORD (National Organization for Rare Disorders).

      Learn more

      These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

      Where to Start

      • MedlinePlus was designed by the National Library of Medicine to help you research your health questions, and it provides more information about this topic.
      • Genetics Home Reference (GHR) contains information on Hypermobile Ehlers-Danlos syndrome. This website is maintained by the National Library of Medicine.
      • The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

        In-Depth Information

        • GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
        • Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
          Ehlers-Danlos Syndrome
          Genetics of Ehlers-Danlos Syndrome
        • MeSH® (Medical Subject Headings) is a terminology tool used by the National Library of Medicine. Click on the link to view information on this topic.
        • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
        • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
        • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
        • PubMed is a searchable database of medical literature and lists journal articles that discuss Hypermobile Ehlers-Danlos syndrome. Click on the link to view a sample search on this topic.

          References

          1. Levy HP. Ehlers-Danlos Syndrome, Hypermobility Type. GeneReviews. 2018; https://www.ncbi.nlm.nih.gov/books/NBK1279/.
          2. Pauker SP & Stoler J. Clinical manifestations and diagnosis of Ehlers-Danlos syndromes. UpToDate. 2018; https://www.uptodate.com/contents/clinical-manifestations-and-diagnosis-of-ehlers-danlos-syndromes.
          3. Pauker SP & Stoler J. Overview of the management of Ehlers-Danlos syndromes. UpToDate. 2016; https://www.uptodate.com/contents/overview-of-the-management-of-ehlers-danlos-syndromes.
          4. Pauker SP & Stoler J. Clinical manifestations and diagnosis of Ehlers-Danlos syndromes. UpToDate. February 22, 2016; https://www.uptodate.com/contents/clinical-manifestations-and-diagnosis-of-ehlers-danlos-syndromes.
          5. Nelson AD, Mouchli MA, Valentin N, Deyle D, Pichurin P, Acosta A, Camilleri M. Ehlers Danlos syndrome and gastrointestinal manifestations: a 20-year experience at Mayo Clinic. Neurogastroenterol Motil. November, 2015; 27(11):1657-1666. https://www.ncbi.nlm.nih.gov/pubmed/26376608.
          6. Brockway L. Gastrointestinal problems in hypermobile Ehlers-Danlos syndrome and hypermobility spectrum disorders. Ehlers-Danlos Support UK. January 4, 2016; https://www.ehlers-danlos.org/information/gastrointestinal-problems-in-hypermobile-ehlers-danlos-syndrome-and-hypermobility-spectrum-disorders/.
          7. Yamada K, Watanabe A, Takeshita H, Fujita A, Miyake N, Matsumoto N, Matsumoto KI. Measurement of Serum Tenascin-X in Joint Hypermobility Syndrome Patients. Biol Pharm Bull. 2019; 42(9):1596-1599. https://www.jstage.jst.go.jp/article/bpb/42/9/42_b19-00168/_html/-char/en.
          8. Susan P Pauker, Joan Stoler. Clinical manifestations and diagnosis of Ehlers-Danlos syndromes. UpToDate. Waltham, MA: UpToDate; July, 2016;
          9. Malfait F, Francomano C, Byers P et al. The 2017 international classification of the Ehlers–Danlos syndromes. Am J Med Genet C Semin Med Genet. March, 2017; 175(1):8-26. https://onlinelibrary.wiley.com/doi/10.1002/ajmg.c.31552/full.
          10. Sobey G. Ehlers-Danlos syndrome: how to diagnose and when to perform genetic tests. Arch Dis Child. Jan 2015; 100(1):57-61. https://www.ncbi.nlm.nih.gov/pubmed/24994860.

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